The present invention relates to star polymer compositions, methods of their preparation and uses thereof, particularly water soluble star polymers comprising amphiphilic arms that create a core-shell (hydrophobic-hydrophilic) structure.
Star polymers are an increasingly attractive target for materials research. As used herein, the term “star polymer” is a uni-molecular, globular, soft matter nanoparticle comprising six or more polymer arms emanating from a central core. The uni-molecular micelle type structure overcomes reliance on dynamic self-assembly of independent polymer chains to form stable micellar structures. There are typically two structural classes of star polymer. A “static core” star polymer is constructed from a pre-formed core. The pre-formed core can be molecular or macromolecular. The polymer arms can be synthetically attached to the pre-formed core to produce the star polymer, or the arms can be synthetically grown from the surface of the pre-formed core. A “microgel core” star polymer, on the other hand, is not constructed from a pre-formed core. A microgel core star polymer comprises a core derived from a polymer synthesis, during which the polymer arms of the structure become covalently bound to a growing microgel network. Many examples of star polymer structures that comprise essentially homopolymer arms have been described.
Of specific interest are star polymer structures comprising amphiphilic polymer arms that can effectively form a partitioned hydrophobic environment within the nanoparticle structure in certain solvents. Star polymers comprising amphiphilic polymer arms have been disclosed. Qiao, et al., WO2007/051252 A1, discloses biodegradable star polymers formed by ring opening polymerization of cyclic carbonyl monomers using metal catalysts. Meier et al., WO2007/048423 A1; Lin et al., Biomolecules, vol. 9(10), (2008), pages 2629-36; and An et al., Polymer, vol. 47, (2006), pages 4154-62 describe organic soluble (i.e., non-water soluble) amphiphilic core-shell star polymers. The “shell” portion contains the polymer arms, generally attached to a static core (e.g., dendrimers, pentaerythritol, and the like). The shell has an inner hydrophilic region and an outer hydrophobic region, each of various compositions. Alternatively, Kreutzer et al., Macromolecules, vol. 39(13), (2006), pages 4507-16, and Zhao et al., U.S. Pat. No. 7,265,186 B2, constructed water soluble amphiphilic core-shell star polymers comprising arms that present a hydrophilic outer region of various compositions and a hydrophobic inner region of various compositions, attached to a static core (e.g., dendrimers, pentaerythritol, etc). Fukukawa, et al., Biomacromolecules, vol. 9(4), (2008), pages 1329-39, disclose water soluble star polymers comprising hydrophilic outer and inner shell regions, attached to a microgel core of varying hydrophobicity composed of either poly(ethylene glycol diacrylate) or poly(divinylbenzene). Conversely, Gao, et al., Macromolecules, vol. 41(4), (2008), pages 1118-1125 describe star polymers comprising a hydrophobic outer shell and a hydrophobic inner shell attached to a microgel core.
Known amphiphilic star polymers have one or more of the following drawbacks, particularly when considered for use as carriers of biologically active materials for gene and/or drug delivery: insufficient water solubility, insufficient hydrophilic/hydrophobic balance of the outer shell and inner shell, insufficient biocompatibility and/or biodegradability, and/or structural limitations associated with the use of a static core.